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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Nature genetics, 2022-05, Vol.54 (5), p.560-572 [Peer Reviewed Journal]

2022. The Author(s), under exclusive licence to Springer Nature America, Inc. ;Copyright Nature Publishing Group May 2022 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 1061-4036 ;ISSN: 1546-1718 ;EISSN: 1546-1718 ;DOI: 10.1038/s41588-022-01058-3 ;PMID: 35551307

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Title:
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
Author: Mahajan, Anubha ; Petty, Lauren E ; Chiou, Joshua ; Miguel-Escalada, Irene ; Nakatochi, Masahiro ; Huerta-Chagoya, Alicia ; Bielak, Lawrence F ; Hai, Yang ; Kals, Mart ; Grarup, Niels ; Wuttke, Matthias ; Nousome, Darryl ; Long, Jirong ; Ahmad, Meraj ; Jensen, Richard A ; An, Ping ; Cade, Brian E ; Abaitua, Fernando ; Akiyama, Masato ; Bertoni, Alain ; Bian, Zheng ; Brummett, Chad M ; Chee, Miao-Li ; Das, Swapan K ; Du, Shufa ; Duan, Qing ; Eckardt, Kai-Uwe ; Fischer, Krista ; Floyd, James S ; Genter, Pauline ; González-Villalpando, Maria Elena ; Gordon-Larsen, Penny ; Gorkin, David ; Herder, Christian ; Hung, Yi-Jen ; Hwu, Chii-Min ; Ikram, Mohammad Arfan ; Ingelsson, Martin ; Islam, Md Tariqul ; Isono, Masato ; Kamatani, Yoichiro ; Katsuya, Tomohiro ; Khor, Chiea-Chuen ; Kohara, Katsuhiko ; Kriebel, Jennifer ; Kuusisto, Johanna ; Läll, Kristi ; Leong, Aaron ; Luan, Jian'an ; Lv, Jun ; Lyssenko, Valeriya ; Meitinger, Thomas ; Morris, Andrew D ; Nadkarni, Girish N ; Nayak, Uma ; Ntalla, Ioanna ; Peters, Annette ; Preissl, Sebastian ; Rasmussen-Torvik, Laura J ; Roden, Michael ; Sabanayagam, Charumathi ; Schönherr, Sebastian ; Shahriar, Mohammad ; Shi, Jinxiu ; Stančáková, Alena ; Strauch, Konstantin ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Tsai, Fuu-Jen ; Tusie-Luna, Teresa ; Udler, Miriam S ; Valladares-Salgado, Adan ; Yajnik, Chittaranjan S ; Yoon, Kyungheon ; Igase, Michiya ; Hanis, Craig L ; Ingelsson, Erik ; Zeggini, Eleftheria ; Rich, Stephen S ; Kooperberg, Charles ; Engert, James C ; Wilson, James G ; Kardia, Sharon L R ; Groop, Leif ; Bharadwaj, Dwaipayan ; Sale, Michèle M ; Cruz, Miguel ; Tai, E-Shyong ; Kato, Norihiro ; Laakso, Markku ; Köttgen, Anna ; Loos, Ruth J F ; Saleheen, Danish ; Hansen, Torben ; Kadowaki, Takashi ; Walters, Robin G ; Stefansson, Kari ; Meigs, James B ; Gloyn, Anna L ; Chambers, John C
Subjects: ancestry group ; Basic Medicine ; comparative study ; Conditional probability ; Consortia ; controlled study ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 ; Diabetes Mellitus, Type 2 - epidemiology ; disease risk assessment ; Ethnic factors ; Ethnicity ; Gene mapping ; genetic association ; genetic background ; genetic heterogeneity ; genetic predisposition ; Genetic Predisposition to Disease ; genetic risk score ; genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Health risk assessment ; Hispanic people ; human ; Humans ; Life Sciences ; Localization ; major clinical study ; Mapping ; Medical and Health Sciences ; Medical Genetics ; Medicin och hälsovetenskap ; Medicinsk genetik ; Medicinska och farmaceutiska grundvetenskaper ; Meta-analysis ; missense mutation ; Molecular modelling ; multiomics ; non insulin dependent diabetes mellitus ; Polymorphism, Single Nucleotide ; Polymorphism, Single Nucleotide - genetics ; Population ; population genetics ; Population studies ; Populations ; Public health ; quantitative trait locus ; risk factor ; Risk Factors ; single nucleotide polymorphism ; Translation
Is Part Of: Nature genetics, 2022-05, Vol.54 (5), p.560-572
Description: We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10 ), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.
Publisher: United States: Nature Publishing Group
Language: English
Identifier: ISSN: 1061-4036
ISSN: 1546-1718
EISSN: 1546-1718
DOI: 10.1038/s41588-022-01058-3
PMID: 35551307
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
ProQuest Central

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Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

2022. The Author(s), under exclusive licence to Springer Nature America, Inc. ;Copyright Nature Publishing Group May 2022 ;Distributed under a Creative Commons Attribution 4.0 International License ;ISSN: 1061-4036 ;ISSN: 1546-1718 ;EISSN: 1546-1718 ;DOI: 10.1038/s41588-022-01058-3 ;PMID: 35551307

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